Process for the preparation of 2-aminoalkane-1,3,4-triols

Abstract

The subject of the invention is a process for the preparation of 2-aminoalkane-1,3,4-triols, in a single stage, preferably a single reduction state, from alkyl 2-hydroxyimino-3-oxo-4-acyloxyalkanoates. The invention makes possible a significant reduction in the number of stages and a marked improvement in the synthesis yields.

We claim: 
     
       1. A method for the preparation of a 2-aminoalkane-1,3,4-triol or a salt thereof, comprising the step of converting in a single reduction stage an alkyl 2-hydroxyimino-3-oxo-4-acyloxyalkanoate of formula (I): ##STR4## in which R 1  represents an alkyl, alkenyl or aralkyl radical, each of which radicals is linear or branched, optionally interrupted by ether bridges, optionally hydroxylated, and optionally a carrier of a C 1  to C 8  acyloxy functional group, and wherein said alkyl, alkenyl, and aralkyl radicals comprise 4 to 28 carbon atoms, R 2  represents an alkyl or alkenyl radical, each of which radicals is linear or branched and optionally interrupted by ether bridges, wherein said alkyl radical comprises 1 to 5 carbon atoms and wherein said alkenyl radical comprises 2 to 5 carbon atoms,   R 3  represents an alkyl, alkenyl or aryl radical, each of which alkyl and alkenyl radicals is linear or branched, and wherein said alkyl radical comprises 1 to 6 carbon atoms, and wherein said alkenyl radical comprises 2 to 6 carbon atoms, and wherein said aryl radical comprises 3 to 6 carbon atoms,   to a 2-aminoalkane-1,3,4-triol or a salt thereof.   
     
     
       2. A method according to claim 1, wherein said converting step occurs in at least one solvent. 
     
     
       3. A method according to claim 1, wherein said converting step occurs in the presence of at least one hydride. 
     
     
       4. A method according to claim 2, wherein said converting step occurs in the presence of at least one hydride. 
     
     
       5. A method according to claim 1, wherein as a result of said converting step, said 2-aminoalkane-1,3,4-triol or salt thereof is present in a reaction mixture. 
     
     
       6. A method according to claim 1, wherein R 1  is an optionally hydroxylated alkyl or alkenyl radical having from 8 to 20 carbon atoms. 
     
     
       7. A method according to claim 1, wherein R 2  is a methyl or ethyl radical. 
     
     
       8. A method according to claim 1, wherein R 3  is a methyl or phenyl radical. 
     
     
       9. A method according to claim 2, wherein said solvent is an anyhdrous solvent. 
     
     
       10. A method according to claim 2, wherein said at least one solvent is selected from toluene, heptane, tetrahydrofuran, tert-butyl methyl ether and isopropyl ether. 
     
     
       11. A method according to claim 2, wherein said at least one solvent is tert-butyl methyl ether. 
     
     
       12. A method according to claim 1, wherein said converting step is carried out in an inert atmosphere. 
     
     
       13. A method according to claim 12, wherein said inert atmosphere comprises argon. 
     
     
       14. A method according to claim 3, wherein said at least one hydride is selected from lithium aluminum hydride and sodium bis(2-methoxyethoxy)-aluminimum hydride. 
     
     
       15. A method according to claim 3, wherein said at least one hydride is sodium bis(2-methoxyethoxy)aluminum hydride. 
     
     
       16. A method according to claim 3, wherein said at least one hydride is present in a concentration ranging from 3 to 7 molar equivalents with respect to the alkyl 2-hydroxyimino-3-oxo-4-acyloxyalkanoate. 
     
     
       17. A method according to claim 2, wherein said converting step is initiated at a controlled starting temperature and is then continued at any temperature ranging from -10° C. to the reflux temperature of said solvent. 
     
     
       18. A method according to claim 2, wherein said converting step, once initiated, is continued at the reflux temperature of the solvent. 
     
     
       19. A method according to claim 1, wherein said converting step is initiated at a temperature of 0° C. 
     
     
       20. A method according to claim 5, further comprising, after said converting step, the step of adjusting the pH of said reaction mixture to less than 2 or greater than 11. 
     
     
       21. A method according to claim 20, wherein, after said adjusting step, the pH of said reaction mixture is approximately 1. 
     
     
       22. A method according to claim 20, wherein, after said adjusting step, the pH of said reaction mixture is approximately 12. 
     
     
       23. A method according to claim 20, wherein said reaction mixture is adjusted to a pH of less than 2 using hydrochloric acid. 
     
     
       24. A method according to claim 20, wherein said reaction mixture is adjusted to a pH of greater than 11 using sodium hydroxide. 
     
     
       25. A method for the preparation of a ceramide, comprising: preparing a 2-aminoalkane-1,3,4-triol or a salt thereof according to the method of claim 1; and   acylating the amino functional group of said 2-aminoalkane-1,3,4-triol or a salt thereof to obtain a ceramide.   
     
     
       26. A method according to claim 25, wherein said 2-aminoalkane-1,3,4-triol or salt thereof is acylated by at least one acylating agent selected from an acid chloride, an anhydride, a para-nitrophenol ester, a succinimide ester, a dicyclohexylcarbodiimide ester, a lower alkyl ester and an azolide. 
     
     
       27. A method according to claim 25, wherein said acylating step is performed in an anhydrous medium or in at least one solvent. 
     
     
       28. A method according to claim 27, wherein said at least one solvent is selected from tetrahydrofuran, pyridine, dimethylformamide and dichloromethane. 
     
     
       29. A method according to claim 26, wherein said anhydride is a mixed anhydride, said lower alkyl ester is a methyl or ethyl ester and said azolide is an imidazolide or a pyrazolide.